Hydrocortisone is used in many topical preparations as a treatment for temporary relief of itching associated with minor skin irritation, inflammation and rashes due to eczema, insect bites, poison ivy, poison oak, poison sumac, soaps, detergents, cosmetics, seborrheic dermatitis, psoriasis and itching in the genital and anal areas of the body. Hydrocortisone has limited solubility in water. Thus, it is necessary to add co-solvents, surfactants, and/or complexing agents to obtain an aqueous solution of hydrocortisone in sufficient concentration to be therapeutically efficacious.
U.S. Pat. No. 2,880,130 discloses the use of polyoxyethylene sorbitan monooleate (Tween 80®) in amounts of from 2-25 percent of the vehicle to obtain clear aqueous solutions containing up to 0.2% of hydrocortisone. U.S. Pat. No. 4,289,764 describes formulations containing 0.025 to 0.4% hydrocortisone in an aqueous solution of 15-50% propylene glycol that is acidified to pH 2.7-3.3 with a non-toxic organic acid such as citric acid. U.S. Pat. No. 4,305,936 provides for a 0.005-2.5% hydrocortisone clear liquid formulation containing 1-4% by weight of a glyceryl ester of fatty acids having 6-22 carbon atoms, 1-3% by weight of the hydrocortisone of a betaine surfactant, and 10-50% of an alkanol co-solvent, preferably ethanol. U.S. Pat. No. 4,778,060 describes a 0.5% hydrocortisone aqueous solution for use as a douche and for impregnating towelettes for wipes. The solution also contains caprylic/capric triglycerides (5-20%), sorbitan stearate (2-4%), Polysorbate 60® (1-3%), preservatives and citric acid.
U.S. Pat. No. 4,383,992 discloses an aqueous solution of an inclusion complex of unbranched beta-cyclodextrin and hydrocortisone and reveals that the inclusion complex must dissociate before the hydrocortisone is physiologically active. U.S. Pat. No. 5,229,370 discloses an aqueous solution on an inclusion complex composed of a branched beta-cyclodextrin and hydrocortisone. U.S. Pat. No. 4,853,379 teaches hydrocortisone compositions containing a mixture of solvents which are an aliphatic alcohol, propylene glycol and dimethyl coco-benzylammoniurn chloride. U.S. Pat. No. 4,971,789 teaches various ionic polyethers as solubilizers for pharmaceuticals such as hydrocortisone. U.S. Pat. No. 5,190,936 teaches compositions containing hydrocortisone and a lipid phase of nonionic amphiphilic lipid vesicles. GB 2,131,693 teaches hydrocortisone compositions containing a solvent mixture of (i) a caprolactam and (ii) 2-isostearyl-1-hyroxylethyl-1-benzylimidazolinium chloride or an alkylphenol polyglycerol. WO 96/20712 teaches aqueous solutions of hydrocortisone free of lower alcohols that contain sodium dioctyl sulfosuccinate in mixtures of glycerin, propylene glycol and polyethylene glycol.